tbuckley/cabot-search huggingface dataset:
Abstract 9904: Ability of Comprehensive Assessment of Strain Dyssynchrony Index by Speckle Tracking Imaging to Predict Long-Term Outcome After Cardiac Resynchronization Therapy in Patients with Heart Failure
Authors: Kazuhiro Tatsumi, Hidekazu Tanaka, Tatsuya Miyoshi, Mana Hiraishi, Akihiro Kaneko, Takayuki Tsuji, Keiko Ryo, Yuko Fukuda, Kensuke Matsumoto, Akihiro Yoshida, Hiroya Kawai, Ken-ichi Hirata
Journal: Circulation (2011)

Background: We previously reported that a combined assessment of radial, circumferential, and longitudinal strain dyssynchrony index (SDI) can further enhance the ability of the method to predict left ventricular reverse remodeling short-term after cardiac resynchronization therapy (CRT). Hypothesis: SDI can predict long-term outcome after CRT in patients with heart failure (HF). Methods: We studied 64 HF patients who underwent CRT. SDI was calculated as the average difference between peak and end-systolic strain from 6-segment for radial and circumferential SDIs and 18-segment for longitudinal SDI using two-dimensional speckle-tracking strain. On the basis of our previous observations, pre-defined cutoff for significant dyssynchrony and residual myocardial contractility was radial SDI ≥6.5%, circumferential SDI ≥3.2%, and longitudinal SDI ≥3.6%. The pre-defined principal outcome variable was the combined endpoint of death from worsening HF and re-hospitalization for deteriorating HF. Long-term follow-up after CRT was tracked over 3.5 years. Results: The primary endpoint of a pre-specified clinical event occurred in 15 patients (23%). Patients with significant radial, circumferential, and longitudinal SDIs were associated with favorable long-term outcome after CRT (p&lt;0.001, &lt;0.005, and &lt;0.01 vs. patients without significant SDIs, respectively). Furthermore, long-term outcome after CRT in patients with positivity 3 of 3 types of SDIs was better than that in patients with positivity either 1 or none of 3SDIs (p&lt;0.005 and &lt;0.001). Cardiovascular event-free rate in patients with positivity 3 of 3 SDIs was also higher than that in patients with positivity none of 3SDIs (100% vs. 30%, p&lt;0.001). Conclusions: SDIs can successfully predict long-term outcome after CRT in HF patients. Moreover, the combined approach leads to more accurate prediction than using individual parameters, and these observations may have clinical implications in CRT patients.
Titanium Culture Vessel Presenting Temperature Gradation for the Thermotolerance Estimation of Cells
Authors: Chikahiro Imashiro, Yangyan Jin, Motoaki Hayama, Takahiro G. Yamada, Akira Funahashi, Katsuhisa Sakaguchi, Shinjiro Umezu, Jun Komotori
Journal: Cyborg and Bionic Systems (2023)

Hyperthermia can be induced to exploit the thermal intolerance of cancer cells, which is worse than that of normal cells, as a potential noninvasive cancer treatment. To develop an effective hyperthermia treatment, thermal cytotoxicity of cells should be comprehensively investigated. However, to conduct such investigations, the culture temperature must be accurately regulated. We previously reported a culture system in which the culture temperature could be accurately regulated by employing metallic culture vessels. However, appropriate temperature conditions for hyperthermia depend on the cell species. Consequently, several experiments need to be conducted, which is a bottleneck of inducing hyperthermia. Hence, we developed a cell culture system with temperature gradation on a metallic culture surface. Michigan Cancer Foundation-7 cells and normal human dermal fibroblasts were used as cancer and normal cell models, respectively. Normal cells showed stronger thermal tolerance; this was because the novel system immediately exhibited a temperature gradation. Thus, the developed culture system can be used to investigate the optimum thermal conditions for effective hyperthermia treatment. Furthermore, as the reactions of cultured cells can be effectively assessed with the present results, further research involving the thermal stimulation of cells is possible.
Biomanufacturing of 3D Tissue Constructs in Microgravity and their Applications in Human Pathophysiological Studies
Authors: Zhanping Ren, Anicca D. Harriot, Devin B. Mair, Michael K. Chung, Peter H. U. Lee, Deok‐Ho Kim
Journal: Advanced Healthcare Materials (2023)

The growing interest in bioengineering in-vivo-like 3D functional tissues has led to novel approaches to the biomanufacturing process as well as expanded applications for these unique tissue constructs. Microgravity, as seen in spaceflight, is a unique environment that may be beneficial to the tissue-engineering process but cannot be completely replicated on Earth. Additionally, the expense and practical challenges of conducting human and animal research in space make bioengineered microphysiological systems an attractive research model. In this review, published research that exploits real and simulated microgravity to improve the biomanufacturing of a wide range of tissue types as well as those studies that use microphysiological systems, such as organ/tissue chips and multicellular organoids, for modeling human diseases in space are summarized. This review discusses real and simulated microgravity platforms and applications in tissue-engineered microphysiological systems across three topics: 1) application of microgravity to improve the biomanufacturing of tissue constructs, 2) use of tissue constructs fabricated in microgravity as models for human diseases on Earth, and 3) investigating the effects of microgravity on human tissues using biofabricated in vitro models. These current achievements represent important progress in understanding the physiological effects of microgravity and exploiting their advantages for tissue biomanufacturing.
Updates in chronic graft‐versus‐host disease management
Authors: Florent Malard, Mohamad Mohty
Journal: American Journal of Hematology (2023)

Abstract Chronic graft‐versus‐host disease (cGvHD) remains the most important long‐term complication of allogeneic hematopoietic cell transplantation (allo‐HCT), but the field has seen significant changes in the last decade. Remarkable advances in the understanding of the biological pathways of cGvHD, lead to the development of targeted therapy with novel drugs thereby minimizing the exposure to harmful corticosteroids, preserving function and mobility, preventing disability, and improving quality of life (QoL) and overall survival (OS). Steroid‐refractory cGvHD management has recently experienced significant improvement since ibrutinib and ruxolitinib were approved for patients that failed at least one line of treatment and belumosudil for patients that failed two lines. These recently approved drugs will be discussed in this review, along with perspectives regarding cGVHD management and additional promising drug in development.
Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial
Authors: Maria-Luisa Schubert, Anita Schmitt, Angela Hückelhoven-Krauss, Brigitte Neuber, Alexander Kunz, Philip Waldhoff, Dominik Vonficht, Schayan Yousefian, Lea Jopp-Saile, Lei Wang, Felix Korell, Anna Keib, Birgit Michels, Dominik Haas, Tim Sauer, Patrick Derigs, Andreas Kulozik, Joachim Kunz, Petra Pavel, Sascha Laier, Patrick Wuchter, Johann Schmier, Gesine Bug, Fabian Lang, Nicola Gökbuget, Jochen Casper, Martin Görner, Jürgen Finke, Andreas Neubauer, Mark Ringhoffer, Denise Wolleschak, Monika Brüggemann, Simon Haas, Anthony D. Ho, Carsten Müller-Tidow, Peter Dreger, Michael Schmitt
Journal: Journal of Hematology & Oncology (2023)

Abstract Background Third-generation chimeric antigen receptor (CAR)-engineered T cells (CARTs) might improve clinical outcome of patients with B cell malignancies. This is the first report on a third-generation CART dose-escalating, phase-1/2 investigator-initiated trial treating adult patients with refractory and/or relapsed (r/r) acute lymphoblastic leukemia (ALL). Methods Thirteen patients were treated with escalating doses of CD19-directed CARTs between 1 × 10 6 and 50 × 10 6 CARTs/m 2 . Leukapheresis, manufacturing and administration of CARTs were performed in-house. Results For all patients, CART manufacturing was feasible. None of the patients developed any grade of Immune effector cell-associated neurotoxicity syndrome (ICANS) or a higher-grade (≥ grade III) catokine release syndrome (CRS). CART expansion and long-term CART persistence were evident in the peripheral blood (PB) of evaluable patients. At end of study on day 90 after CARTs, ten patients were evaluable for response: Eight patients (80%) achieved a complete remission (CR), including five patients (50%) with minimal residual disease (MRD)-negative CR. Response and outcome were associated with the administered CART dose. At 1-year follow-up, median overall survival was not reached and progression-free survival (PFS) was 38%. Median PFS was reached on day 120. Lack of CD39-expression on memory-like T cells was more frequent in CART products of responders when compared to CART products of non-responders. After CART administration, higher CD8 + and γδ-T cell frequencies, a physiological pattern of immune cells and lower monocyte counts in the PB were associated with response. Conclusion In conclusion, third-generation CARTs were associated with promising clinical efficacy and remarkably low procedure-specific toxicity, thereby opening new therapeutic perspectives for patients with r/r ALL. Trial registration This trial was registered at www.clinicaltrials.gov as NCT03676504.
The ubiquitin‐specific protease 5 mediated deubiquitination of LSH links metabolic regulation of ferroptosis to hepatocellular carcinoma progression
Authors: Bokang Yan, Jiaxing Guo, Zuli Wang, Jieling Ning, Haiyan Wang, Long Shu, Kuan Hu, Ling Chen, Ying Shi, Lingqiang Zhang, Shuang Liu, Yongguang Tao, Desheng Xiao
Journal: MedComm (2023)

Epigenetic regulators and posttranslational modifications of proteins play important roles in various kinds of cancer cell death, including ferroptosis, a non-apoptotic form of cell death. However, the interplay of chromatin modifiers and deubiquitinase (DUB) in ferroptosis remains unclear. Here, we found that ubiquitin-specific protease 5 (USP5) is regarded as a bona fide DUB of lymphoid-specific helicase (LSH), a DNA methylation repressor, in hepatocellular carcinoma (HCC). Functional studies reveal that USP5 interacts with LSH and stabilizes LSH by a deubiquitylation activity-dependent process. Furthermore, the USP5-mediated deubiquitination of LSH facilitates the tumorigenesis of HCC by upregulating solute carrier family 7 member 11 (SLC7A11) to suppress ferroptosis of liver cancer cells. Moreover, the USP5 inhibitor degrasyn inhibits DUB activities of USP5 to LSH to suppress the progression of HCC. Additionally, USP5 and LSH are positively correlated and both are overexpressed and linked to poor prognosis in HCC patients. Together, our findings show that USP5 interacts with LSH directly and enhances LSH protein stability through deubiquitination, which, in turn, promotes the development of HCC by suppressing ferroptosis of liver cancer cells, suggesting that USP5 may be a potential therapeutic target for HCC.
EGFR expression is associated with relapse in a melanoma cohort receiving adjuvant PD-1-based immunotherapy
Authors: Teresa Amaral, Oltin Tiberiu Pop, Eftychia Chatziioannou, Tobias Sinnberg, Heike Niessner, Jing Zhao, Sandra Stephanie Ring, Markus Joerger, Christopher Schroeder, Sorin Armeanu-Ebinger, Antonio Cozzio, Ulrike Leiter, Ioannis Thomas, Wolfram Jochum, Claus Garbe, Stephan Forchhammer, Mitchell Levesque, Joanna Mangana, Michael Hölzel, Reinhard Dummer, Christian M. Schürch, Andrea Forschner, Lukas Flatz
Journal: Journal of the American Academy of Dermatology (2023)
Extracellular vesicle-circEHD2 promotes the progression of renal cell carcinoma by activating cancer-associated fibroblasts
Authors: Tao He, Qiansheng Zhang, Peng Xu, Wen Tao, Fuyang Lin, Renfei Liu, Mingzhao Li, Xiaolu Duan, Chao Cai, Di Gu, Guohua Zeng, Yongda Liu
Journal: Molecular Cancer (2023)

Abstract Background The encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement of various tumors. However, the regulatory role of EVs-circRNA in renal cell carcinoma (RCC) remains elusive. Methods The in vitro and in vivo functional experiments were implemented to measure the effects of circEHD2 on the phenotype of RCC. The functional role of EVs-circEHD2 on the activation of fibroblasts was assessed by collagen contraction assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). The mechanism was investigated by RNA pull-down assay, RNA immunoprecipitation, chromatin isolation by RNA purification, luciferase assay, and co-immunoprecipitation assay. Results We demonstrated that circEHD2 was upregulated in RCC tissues and serum EVs of RCC patients with metastasis. Silencing circEHD2 inhibited tumor growth in vitro and in vivo. Mechanistic studies indicated that FUS RNA -binding protein (FUS) accelerated the cyclization of circEHD2, then circEHD2 interacts with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH), which acts as a bridge to recruit circEHD2 and Yes1-associated transcriptional regulator (YAP) to the promoter of SRY-box transcription factor 9 (SOX9); this results in the sustained activation of SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates the package of circEHD2 into EVs, then EVs-circEHD2 transmits to fibroblasts, converting fibroblasts to cancer-associated fibroblasts (CAFs). Activated CAFs promote the metastasis of RCC by secreting pro-inflammatory cytokines such as IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting circEHD2 exhibited a strong inhibition of tumor growth in vivo. Conclusions The circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates the growth of RCC. EVs-circEHD2 facilitates the metastasis of RCC by converting fibroblasts to CAFs. Our results suggest that EVs-circEHD2 may be a useful biomarker and therapeutic target for RCC.
A pilot study of camrelizumab with docetaxel and cisplatin for the first line treatment in recurrent/metastatic oral squamous cell carcinoma
Authors: Houyu Ju, Dongliang Wei, Yunteng Wu, Yang Liu, Qi Ding, Mengyu Rui, Zongyu Fan, Yanli Yao, Jingzhou Hu, Guoxin Ren
Journal: MedComm (2023)

Pembrolizumab with cisplatin and 5-fluorouracil showed survival benefit but relatively high occurrence of treatment-related adverse events (TRAEs) for recurrent/metastatic oral squamous cell carcinoma (R/M OSCC). A more tolerable regime is needed. This trial enrolled 20 R/M OSCC patients with previously untreated and PD-L1 positive. Patients were administered camrelizumab with docetaxel and cisplatin every 3 weeks for six cycles, followed by camrelizumab monotherapy every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was occurrence of grade ≥ 3 TRAEs, secondary endpoints included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). 45% patients experienced grade ≥ 3 TRAEs, which the most common were anemia (15%), stomatitis (15%), and neutropenia (10%). The most common potential immune-related adverse events were reactive cutaneous capillary endothelial proliferation (RCCEP; 60%), hypothyroidism (35%), and pneumonitis (15%). No treatment-related deaths occurred. The median OS, PFS, and ORR was 14.4 months, 5.35 months, and 40.0% respectively. The study also found RCCEP occurrence, lower FOXP3
Tubular cell transcriptional intermediary factor 1γ deficiency exacerbates kidney injury-induced tubular cell polyploidy and fibrosis
Authors: Chaoyi Yuan, Guannan Jin, Pengcheng Li, Wei Wang, Chang Ge, Yonglong Pan, Qiaofeng Zhang, Jie Mo, Dong Kuang, Liu Liu, Xuewu Zhang, Huifang Liang, Wanguang Zhang, Xi Tang, Zifu Li, Jihong Liu, Gang Xu, Xiaoping Chen, Ze-yang Ding, Bixiang Zhang
Journal: Kidney International (2023)
Turquoise killifish: A natural model of age-dependent brain degeneration
Authors: Dennis E.M. de Bakker, Dario R. Valenzano
Journal: Ageing Research Reviews (2023)

Turquoise killifish (Nothobranchius furzeri) are naturally short-lived vertebrates that display a wide range of spontaneous age-related changes, including onset of cancer, reduced mobility, and cognitive decline. Here, we focus on describing the phenotypic spectrum of the aging killifish brain. As turquoise killifish age, their dopaminergic and noradrenergic neurons undergo a significant decline in number. Furthermore, brain aging in turquoise killifish is associated with several glial-specific changes, such as an increase in the astrocyte-covered surface area and an increase in the numbers of microglial cells, i.e. the brain-specific macrophage population. Killifish brains undergo age-dependent reduced proteasome activity and increased protein aggregation, including the aggregation of the Parkinson's disease marker α-synuclein. Parallel to brain degeneration, turquoise killifish develop spontaneous age-related gut dysbiosis, which has been proposed to affect human neurodegenerative disease. Finally, aged turquoise killifish display declined learning capacity. We argue that, taken together, the molecular, cellular and functional changes that spontaneously take place during aging in killifish brains are consistent with a robust degenerative process that shares remarkable similarities with human neurodegenerative diseases. Hence, we propose that turquoise killifish represent a powerful model of spontaneous brain degeneration which can be effectively used to explore the causal mechanisms underlying neurodegenerative diseases.
Adenosine receptor signalling as a driver of pulmonary fibrosis
Authors: Emily Cash, Amanda T. Goodwin, Amanda L. Tatler
Journal: Pharmacology & Therapeutics (2023)

Pulmonary fibrosis is a debilitating and life-limiting lung condition in which the damage- response mechanisms of mixed-population cells within the lungs go awry. The tissue microenvironment is drastically remodelled by aberrantly activated fibroblasts which deposit ECM components into the surrounding lung tissue, detrimentally affecting lung function and capacity for gas exchange. Growing evidence suggests a role for adenosine signalling in the pathology of tissue fibrosis in a variety of organs, including the lung, but the molecular pathways through which this occurs remain largely unknown. This review explores the role of adenosine in fibrosis and evaluates the contribution of the different adenosine receptors to fibrogenesis. Therapeutic targeting of the adenosine receptors is also considered, along with clinical observations pointing towards a role for adenosine in fibrosis. In addition, the interaction between adenosine signalling and other profibrotic signalling pathways, such as TGFβ1 signalling, is discussed.
Vasospastic angina: Past, present, and future
Authors: Zuowen He, Xin Xu, Qu Zhao, Hu Ding, Dao Wen Wang
Journal: Pharmacology & Therapeutics (2023)

Vasospastic angina (VSA) is characterized by episodes of rest angina that are responsive to short-acting nitrates and are attributable to coronary artery vasospasm. The condition is underdiagnosed as the provocation test is rarely performed. VSA, the most important component of non-obstructive coronary artery disease, can present with angina, be asymptomatic, or can even present with fatal arrhythmias and cardiac arrest. Although most patients with VSA respond well to vasodilating medications, prognosis does not improve as expected in most patients, suggesting the existence elusive prognostic factors and pathogenesis that warrant further exploration. Moreover, patients with either severe or refractory VSA barely respond to conventional treatment and may develop life-threatening arrhythmias or suffer sudden cardiac death during ischemic attacks, which are associated with immune-inflammatory responses and have been shown to achieve remission following glucocorticoid and immunoglobulin treatments. Our recent work revealed that inflammation plays a key role in the initiation and development of coronary spasms, and that inflammatory cytokines have predictive value for diagnosis. In contrast to the existing literature, this review both summarizes the theoretical and clinical aspects of VSA, and also discusses the relationship between inflammation, especially myocarditis and VSA, in order to provide novel insights into the etiology, diagnosis, and treatment of VSA.
Molecular bases of comorbidities: present and future perspectives
Authors: Jon Sánchez-Valle, Alfonso Valencia
Journal: Trends in Genetics (2023)

Co-occurrence of diseases decreases patient quality of life, complicates treatment choices, and increases mortality. Analyses of electronic health records present a complex scenario of comorbidity relationships that vary by age, sex, and cohort under study. The study of similarities between diseases using 'omics data, such as genes altered in diseases, gene expression, proteome, and microbiome, are fundamental to uncovering the origin of, and potential treatment for, comorbidities. Recent studies have produced a first generation of genetic interpretations for as much as 46% of the comorbidities described in large cohorts. Integrating different sources of molecular information and using artificial intelligence (AI) methods are promising approaches for the study of comorbidities. They may help to improve the treatment of comorbidities, including the potential repositioning of drugs.
A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis
Authors: Ting Zheng, Joelle BouSaba, Ann Taylor, Saam Dilmaghani, Irene Busciglio, Paula Carlson, Monique Torres, Michael Ryks, Duane Burton, William Scott Harmsen, Michael Camilleri
Journal: Clinical Gastroenterology and Hepatology (2023)
Bypassing the cytokine sink: IL-2-independent IL-2 receptor signaling
Authors: Tim Luetkens
Journal: Molecular Therapy (2023)

Harnessing genetically engineered T cells for therapeutic purposes has been the focus of intense preclinical and clinical research over the past decade. However, in many cases, therapeutic T cells struggle to persist in vivo resulting in limited clinical efficacy. Recent research has therefore focused on the development of tools for the selective expansion of engineered T cells in vivo. In this issue, Cook et al. describe such an approach for the selective expansion of regulatory T cells (Tregs) and T cells expressing chimeric antigen receptors (CARs). 1 Cook P.J. Yang S.J. Uenishi G.I. Grimm A. West S.E. Wang L.-J. Jacobs C. Repele A. Drow T. Boukhris A. et al. A chemically inducible IL-2 receptor signaling complex allows for effective in vitro and in vivo selection of engineered CD4+ T cells. Mol. Ther. 2023; https://doi.org/10.1016/j.ymthe.2023.04.021 Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Their technology is based on a chemically inducible signaling complex (CISC), which when triggered by the small molecule drug rapamycin, leads to interleukin-2 (IL2)-independent IL2 receptor (IL2R) signaling and subsequent proliferation of the engineered cells. The work establishes a model of tunable IL2R signaling in engineered T cells and provides proof of concept of this technology in reducing graft-versus-host disease (GvHD) and for the manufacturing of CAR T cells. CISC engineering is a promising new tool to enhance the therapeutic activity of genetically modified T cells.